A series of "in vivo" and "in vitro" studies are proposed which are designed to investigate the tissue interactions that exert an inductive influence, either directive or permissive, on the development of the anlagen of the mammalian inner ear (otocyst), and to examine defects in or the absence of the tissue interactions acting during development that result in the production of a cogenitally-malformed inner ear. These research studies will use a CBA/C57 hybrid mouse as a normal model of inner ear organogenesis, and the homozygotic kreisler (kr/kr) inner ear as a model for congenital malformation of the labyrinth. The inductive tissue interactions which occur between brain (otic area), periotic mesenchyme, otocyst and stato-acoustic ganglion will be studied. These research studies will use the experimental embryological techniques of: organ culture, time lapse cinematography "in vitro", transfilter membrane tissue interaction, light microscopy, radioisotopically-labelled amino acids combined with serial section autoradiography, histochemistry, electron microscopy, experimental embryonic surgery, teratology and genetics. The overall experimental design is such that the results from one section (neural induction) will interlock with the results from another section (epithelial-mesenchymal interaction) to provide a comprehensive understanding of the successive series of inductive tissue interactions that act during labyrinthine development to produce a normal inner ear. This understanding of the inductive sequences in normal inner ear development will serve as a basis for the study of the mechanisms of congenital malformation of the labyrinth.